title: Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs.
abstract: The study was performed to evaluate the percutaneous penetration of ketoprofen after transdermal administration using a microdialysis technique in pigs, in comparison with rats. Ketoprofen release from patches was determined by analysis of the remaining drug content after application to hairless rats and pigs. Skin and knee joint penetration of ketoprofen was tested by microdialysis, and recovery was determined by retrodialysis. Residual rates in hairless rats and pigs were 68.1 ± 1.6% and 81.7 ± 4.4%, respectively, at 10h. The average recoveries of ketoprofen over 480 min in the skin and knee joint cases were 72.0 ± 3.4% and 9.8 ± 6.2% in rats and 72.3 ± 2.5% and 57.6 ± 3.1% in pigs, respectively. In rats, ketoprofen was rapidly absorbed with transdermal administration, with C(max) values of 191.7 ± 76.2 and 35.5 ± 21.7 ng/mL and AUC(0-8h) values of 918.2 ± 577.5 and 195.9 ± 137.1 ngh/mL, respectively, for the skin and knee joint. The C(max) values for the pig were 20.9 ± 18.5 and 3.7 ± 3.0 ng/mL, with AUC(0-8h) values of 73.1 ± 69.2 and 16.1 ± 16.1 ngh/mL. Ketoprofen concentrations within skin and knee joint of non-application sites in rats and pigs were less than 0.8 ng/mL. Transdermal administration of ketoprofen significantly reduced prostaglandin E2 levels in the skin of the application site and showed a tendency for inhibition in the knee joint. We thus demonstrated that topical patches containing ketoprofen can deliver the drug through the skin and knee joint of pigs and rats via direct diffusion, and microdialysis data with the pig may be useful for the prediction of human tissue penetration of drugs with transdermal administration.
authors.affiliation: Research & Development Department, Nipro Patch Co., Ltd., Saitama, Japan. shinkai@nipro-patch.co.jp
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shinkai
authors.forename: Kazuko
authors.initials: K
authors.lastname: Korenaga
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okumura
authors.forename: Hideo
authors.initials: H
authors.lastname: Mizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamauchi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D007660:Ketoprofen / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine; D057968:Transdermal Patch
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen